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Cortisol-Induced Chromatin Remodeling and Gene Expression in Skeletal Muscle of Rainbow Trout: Integrative ATAC-Seq
Rodrigo Zuloaga1,2,3, Camila Garrido2, Luciano Ahumada-Langer2
1Programa de Doctorado en Biotecnología, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile.
Abstract:
Cortisol, the main glucocorticoid in teleost, plays a central role in mediating the physiological response to stress by regulating metabolism, immune function, and growth. While its transcriptional effects are well known, its role in modulating chromatin accessibility in fish skeletal muscle remains poorly understood. In this study, we investigated the epigenomic and transcriptomic changes induced by cortisol in a juvenile rainbow trout's (Oncorhynchus mykiss) skeletal muscle using ATAC-seq and RNA-seq. Fish were treated with a single intraperitoneal dose of cortisol (10 mg/kg) or vehicle, and muscle samples were collected 3 h post-treatment. ATAC-seq analysis revealed a total of 163,802 differentially accessible regions (DARs), with an important enrichment of open regions near transcription start sites and promoters. A total of 1612 and 1746 differentially accessible genes (DAGs) were identified in the cortisol and control groups, respectively. Motif enrichment analysis identified 89 transcription factors to be significantly enriched, among which key stress-responsive regulators such as Fos, AP-1, FoxO1/3, Mef2a/b/c, Klf5/10, and ATF4 were prominently represented. RNA-seq analysis identified 4050 differentially expressed genes (DEGs), with 2204 upregulated genes involved in autophagy, mitophagy, and FoxO signaling, while 1864 downregulated genes were enriched in spliceosome and chromatin remodeling pathways. Integrative analysis revealed 174 overlapping genes between ATAC-seq and RNA-seq datasets, highlighting pathways linked to autophagy and ATP-dependent chromatin remodeling. Four selected DEGs (sesn1, sesn2, cullin3, samtor) were validated by qPCR, showing high concordance with transcriptomic data. These findings provide new insights into cortisol-mediated regulation of chromatin dynamics and gene expression in teleost skeletal muscle and underscore the importance of epigenetic mechanisms in fish stress responses.
